A second polymorph of β-arteether.

The crystal structure of the title compound, C(17)H(28)O(5), reported here is a polymorph of the structure first reported by El-Feraly, Al-Yahya, Orabi, McPhail & McPhail [J. Nat. Prod. (1992). 55, 878-883]. It is a derivative of the anti-malaria compound artemisinin and consists primarily of three substituted ring systems fused together. A cyclo-hexane ring (distorted chair conformation) fused to a tetra-hydro-pyran group (distorted chair) is adjacent to an oxacyclo-heptane unit containing an endo-peroxide bridge, giving the mol-ecule its particular three-dimensional arrangement. The crystal packing is stabilized by inter-molecular C-H⋯O inter-actions between an O atom from the endo-peroxide bridge and H atoms from both the cyclo-hexane and seven-membered oxacyclo-heptane fused rings, as well as between an O atom and H atom from adjacent tetra-hydro-pyran rings. The two polymorphs have the same space group and similar cell parameters for the a and b axes, but significantly different values for the c axis.

Related literature

For the first polymorph of this compound, see: El-Feraly et al. (1992 ▶). For crystal structures of similar compounds, see: Brossi et al. (1988 ▶); Flippen-Anderson et al. (1989 ▶); Karle & Lin (1995 ▶); Li et al. (2006 ▶); Luo et al. (1984 ▶); Yue et al. (2006 ▶); Butcher et al. (2007 ▶); Jasinski et al. (2008 ▶). For biological activity of artemisinin derivatives in vitro and in vivo, see: Grace et al. (1998 ▶); Li et al. (2001 ▶); Maggs et al. (2000 ▶); Yang et al. (1997 ▶). For endo-peroxide sesquiterpene lactone derivatives, see: Saxena et al. (2003 ▶); Venugopalan et al. (1995 ▶); Wu et al. (2001 ▶). For the synthesis of artemisinin and its derivatives, see: Lui et al. (1979 ▶); Liu (1980 ▶); Robert et al. (2001 ▶). For related literature, see: Cremer & Pople (1975 ▶); Lisgarten et al. (1998 ▶); Qinghaosu Research Group (1980 ▶); Shen & Zhuang (1984 ▶); Wu & Li (1995 ▶).

Experimental

Crystal data

C17H28O5

M = 312.39

Trigonal,

a = 10.0253 (6) Å

c = 28.628 (3) Å

V = 2491.8 (3) Å3

Z = 6

Mo Kα radiation

μ = 0.09 mm−1

T = 103 (2) K

0.42 × 0.22 × 0.18 mm

Data collection

Bruker APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.963, T max = 0.984

27842 measured reflections

4935 independent reflections

4517 reflections with I > 2σ(I)

R int = 0.034

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.101

S = 1.04

4935 reflections

203 parameters

H-atom parameters constrained

Δρmax = 0.38 e Å−3

Δρmin = −0.17 e Å−3

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: APEX2; data reduction: SAINT (Bruker, 2006 ▶); program(s) used to solve structure: SHELXS90 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807062812/at2510sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807062812/at2510Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C17H28O5	Z = 6
Mr = 312.39	F000 = 1020
Trigonal, P3221	Dx = 1.249 Mg m−3
Hall symbol: P 32 2"	Mo Kα radiation λ = 0.71073 Å
a = 10.0253 (6) Å	Cell parameters from 5075 reflections
b = 10.0253 (6) Å	θ = 2.4–30.0º
c = 28.628 (3) Å	µ = 0.09 mm−1
α = 90º	T = 103 (2) K
β = 90º	Chunk, colourless
γ = 120º	0.42 × 0.22 × 0.18 mm
V = 2491.8 (3) Å3

Bruker APEXII CCD area-detector diffractometer	4935 independent reflections
Radiation source: fine-focus sealed tube	4517 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.034
T = 103(2) K	θmax = 30.8º
φ and ω scans	θmin = 2.1º
Absorption correction: multi-scan(SADABS; Sheldrick, 1996)	h = −11→14
Tmin = 0.963, Tmax = 0.984	k = −14→14
27842 measured reflections	l = −39→39

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.040	w = 1/[σ2(Fo2) + (0.0551P)2 + 0.4841P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.101	(Δ/σ)max = 0.005
S = 1.05	Δρmax = 0.38 e Å−3
4935 reflections	Δρmin = −0.17 e Å−3
203 parameters	Extinction correction: none
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 2049 Friedel pairs
Secondary atom site location: difference Fourier map

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
O1	0.71973 (10)	0.35233 (10)	−0.03898 (3)	0.01837 (18)
O2	0.57224 (11)	0.39122 (11)	0.01212 (3)	0.01993 (19)
O3	0.47049 (10)	0.15908 (12)	−0.05520 (3)	0.0219 (2)
O4	0.45576 (11)	0.06611 (11)	−0.01350 (3)	0.02042 (19)
O5	0.60247 (12)	0.45429 (11)	0.09195 (3)	0.02137 (19)
C1	0.58206 (14)	0.15089 (14)	0.01942 (4)	0.0169 (2)
C2	0.50124 (14)	0.12064 (15)	0.06716 (4)	0.0182 (2)
H2A	0.4266	0.0075	0.0686	0.022*
C3	0.61370 (16)	0.15728 (16)	0.10811 (4)	0.0222 (3)
H3A	0.6848	0.2699	0.1097	0.027*
H3B	0.5550	0.1246	0.1377	0.027*
C4	0.70709 (16)	0.07586 (16)	0.10279 (4)	0.0232 (3)
H4A	0.7788	0.1028	0.1295	0.028*
H4B	0.6367	−0.0370	0.1031	0.028*
C5	0.79822 (16)	0.12223 (15)	0.05735 (4)	0.0213 (2)
H5A	0.8658	0.2368	0.0574	0.026*
C6	0.68604 (15)	0.07809 (14)	0.01577 (4)	0.0185 (2)
H6A	0.6163	−0.0360	0.0174	0.022*
C7	0.77196 (15)	0.11190 (16)	−0.03110 (4)	0.0221 (3)
H7A	0.8677	0.2129	−0.0287	0.027*
H7B	0.8024	0.0330	−0.0361	0.027*
C8	0.68289 (16)	0.11487 (16)	−0.07417 (4)	0.0235 (3)
H8A	0.5935	0.0104	−0.0791	0.028*
H8B	0.7505	0.1408	−0.1019	0.028*
C9	0.62470 (15)	0.23007 (15)	−0.07075 (4)	0.0204 (2)
C10	0.66650 (14)	0.32307 (14)	0.00757 (4)	0.0162 (2)
H10A	0.7569	0.3776	0.0290	0.019*
C11	0.49721 (16)	0.37047 (16)	0.05576 (4)	0.0204 (3)
H11A	0.4239	0.4102	0.0527	0.024*
C12	0.40444 (15)	0.20099 (16)	0.06911 (4)	0.0204 (2)
H12A	0.3232	0.1506	0.0446	0.024*
C13	0.90173 (19)	0.05086 (19)	0.05316 (6)	0.0329 (3)
H13A	0.9584	0.0664	0.0824	0.049*
H13B	0.9748	0.1002	0.0275	0.049*
H13C	0.8382	−0.0597	0.0469	0.049*
C14	0.62461 (17)	0.30416 (18)	−0.11675 (4)	0.0270 (3)
H14A	0.5651	0.3570	−0.1135	0.040*
H14B	0.5779	0.2247	−0.1409	0.040*
H14C	0.7308	0.3788	−0.1256	0.040*
C15	0.68313 (17)	0.61729 (15)	0.08415 (5)	0.0241 (3)
H15A	0.6102	0.6513	0.0743	0.029*
H15B	0.7612	0.6446	0.0593	0.029*
C16	0.7603 (2)	0.69468 (18)	0.12949 (5)	0.0367 (4)
H16A	0.8216	0.8063	0.1247	0.055*
H16B	0.8277	0.6557	0.1398	0.055*
H16C	0.6817	0.6722	0.1533	0.055*
C17	0.31881 (17)	0.17746 (18)	0.11531 (5)	0.0279 (3)
H17A	0.2512	0.2216	0.1130	0.042*
H17B	0.3935	0.2286	0.1405	0.042*
H17C	0.2569	0.0670	0.1220	0.042*

	U11	U22	U33	U12	U13	U23
O1	0.0161 (4)	0.0163 (4)	0.0141 (4)	0.0017 (3)	0.0008 (3)	−0.0006 (3)
O2	0.0224 (5)	0.0212 (4)	0.0165 (4)	0.0111 (4)	0.0022 (3)	0.0025 (3)
O3	0.0158 (4)	0.0247 (5)	0.0149 (4)	0.0025 (4)	−0.0014 (3)	0.0020 (3)
O4	0.0157 (4)	0.0187 (4)	0.0149 (4)	−0.0004 (3)	−0.0015 (3)	0.0003 (3)
O5	0.0256 (5)	0.0165 (4)	0.0181 (4)	0.0076 (4)	−0.0010 (4)	−0.0004 (3)
C1	0.0143 (5)	0.0152 (5)	0.0134 (5)	0.0015 (4)	−0.0007 (4)	−0.0012 (4)
C2	0.0159 (5)	0.0161 (5)	0.0150 (5)	0.0024 (5)	0.0003 (4)	0.0006 (4)
C3	0.0255 (6)	0.0191 (6)	0.0163 (5)	0.0068 (5)	−0.0032 (5)	0.0007 (4)
C4	0.0220 (6)	0.0184 (6)	0.0217 (6)	0.0046 (5)	−0.0041 (5)	0.0046 (5)
C5	0.0181 (6)	0.0150 (5)	0.0260 (6)	0.0045 (5)	−0.0020 (5)	0.0039 (5)
C6	0.0168 (6)	0.0124 (5)	0.0208 (5)	0.0031 (4)	0.0015 (4)	0.0007 (4)
C7	0.0187 (6)	0.0177 (6)	0.0246 (6)	0.0052 (5)	0.0040 (5)	−0.0009 (5)
C8	0.0209 (6)	0.0209 (6)	0.0200 (6)	0.0040 (5)	0.0019 (5)	−0.0044 (5)
C9	0.0167 (6)	0.0201 (6)	0.0145 (5)	0.0019 (5)	0.0004 (4)	−0.0014 (4)
C10	0.0158 (5)	0.0142 (5)	0.0142 (5)	0.0041 (4)	−0.0009 (4)	0.0001 (4)
C11	0.0202 (6)	0.0210 (6)	0.0171 (5)	0.0083 (5)	−0.0007 (4)	−0.0009 (4)
C12	0.0175 (5)	0.0218 (6)	0.0164 (5)	0.0058 (5)	0.0007 (4)	−0.0004 (5)
C13	0.0279 (8)	0.0321 (8)	0.0408 (8)	0.0166 (7)	0.0010 (6)	0.0085 (6)
C14	0.0254 (7)	0.0309 (7)	0.0147 (5)	0.0066 (6)	−0.0010 (5)	0.0006 (5)
C15	0.0282 (7)	0.0160 (6)	0.0243 (6)	0.0082 (5)	0.0009 (5)	0.0022 (5)
C16	0.0504 (10)	0.0186 (7)	0.0300 (7)	0.0090 (7)	−0.0053 (7)	−0.0018 (6)
C17	0.0240 (7)	0.0294 (7)	0.0229 (6)	0.0079 (6)	0.0055 (5)	−0.0007 (5)

O1—C10	1.4105 (14)	C7—H7A	0.990
O1—C9	1.4386 (15)	C7—H7B	0.990
O2—C11	1.4192 (15)	C8—C9	1.536 (2)
O2—C10	1.4221 (15)	C8—H8A	0.990
O3—C9	1.4122 (16)	C8—H8B	0.990
O3—O4	1.4759 (13)	C9—C14	1.5122 (17)
O4—C1	1.4619 (14)	C10—H10A	1.000
O5—C11	1.4163 (15)	C11—C12	1.5224 (18)
O5—C15	1.4327 (16)	C11—H11A	1.000
C1—C10	1.5330 (16)	C12—C17	1.5295 (17)
C1—C2	1.5399 (16)	C12—H12A	1.000
C1—C6	1.5462 (18)	C13—H13A	0.980
C2—C3	1.5382 (17)	C13—H13B	0.980
C2—C12	1.5412 (19)	C13—H13C	0.980
C2—H2A	1.000	C14—H14A	0.980
C3—C4	1.526 (2)	C14—H14B	0.980
C3—H3A	0.990	C14—H14C	0.980
C3—H3B	0.990	C15—C16	1.512 (2)
C4—C5	1.5225 (18)	C15—H15A	0.990
C4—H4A	0.990	C15—H15B	0.990
C4—H4B	0.990	C16—H16A	0.980
C5—C13	1.532 (2)	C16—H16B	0.980
C5—C6	1.5427 (18)	C16—H16C	0.980
C5—H5A	1.000	C17—H17A	0.980
C6—C7	1.5380 (17)	C17—H17B	0.980
C6—H6A	1.000	C17—H17C	0.980
C7—C8	1.5315 (19)
C10—O1—C9	113.55 (9)	O3—C9—C14	104.63 (11)
C11—O2—C10	116.17 (9)	O1—C9—C14	107.15 (11)
C9—O3—O4	108.17 (9)	O3—C9—C8	111.90 (11)
C1—O4—O3	111.72 (8)	O1—C9—C8	110.02 (10)
C11—O5—C15	113.02 (10)	C14—C9—C8	114.05 (11)
O4—C1—C10	110.01 (10)	O1—C10—O2	105.06 (9)
O4—C1—C2	103.89 (9)	O1—C10—C1	112.44 (9)
C10—C1—C2	110.98 (10)	O2—C10—C1	113.28 (10)
O4—C1—C6	105.93 (9)	O1—C10—H10A	108.6
C10—C1—C6	113.17 (10)	O2—C10—H10A	108.6
C2—C1—C6	112.30 (10)	C1—C10—H10A	108.6
C3—C2—C1	112.25 (10)	O5—C11—O2	111.96 (11)
C3—C2—C12	115.18 (10)	O5—C11—C12	109.68 (10)
C1—C2—C12	109.64 (10)	O2—C11—C12	111.59 (11)
C3—C2—H2A	106.4	O5—C11—H11A	107.8
C1—C2—H2A	106.4	O2—C11—H11A	107.8
C12—C2—H2A	106.4	C12—C11—H11A	107.8
C4—C3—C2	111.63 (11)	C11—C12—C17	111.82 (12)
C4—C3—H3A	109.3	C11—C12—C2	112.41 (10)
C2—C3—H3A	109.3	C17—C12—C2	113.72 (11)
C4—C3—H3B	109.3	C11—C12—H12A	106.1
C2—C3—H3B	109.3	C17—C12—H12A	106.1
H3A—C3—H3B	108.0	C2—C12—H12A	106.1
C5—C4—C3	110.91 (11)	C5—C13—H13A	109.5
C5—C4—H4A	109.5	C5—C13—H13B	109.5
C3—C4—H4A	109.5	H13A—C13—H13B	109.5
C5—C4—H4B	109.5	C5—C13—H13C	109.5
C3—C4—H4B	109.5	H13A—C13—H13C	109.5
H4A—C4—H4B	108.0	H13B—C13—H13C	109.5
C4—C5—C13	111.57 (11)	C9—C14—H14A	109.5
C4—C5—C6	109.36 (11)	C9—C14—H14B	109.5
C13—C5—C6	111.87 (12)	H14A—C14—H14B	109.5
C4—C5—H5A	108.0	C9—C14—H14C	109.5
C13—C5—H5A	108.0	H14A—C14—H14C	109.5
C6—C5—H5A	108.0	H14B—C14—H14C	109.5
C7—C6—C5	111.24 (11)	O5—C15—C16	107.69 (11)
C7—C6—C1	112.97 (10)	O5—C15—H15A	110.2
C5—C6—C1	112.30 (10)	C16—C15—H15A	110.2
C7—C6—H6A	106.6	O5—C15—H15B	110.2
C5—C6—H6A	106.6	C16—C15—H15B	110.2
C1—C6—H6A	106.6	H15A—C15—H15B	108.5
C8—C7—C6	116.04 (11)	C15—C16—H16A	109.5
C8—C7—H7A	108.3	C15—C16—H16B	109.5
C6—C7—H7A	108.3	H16A—C16—H16B	109.5
C8—C7—H7B	108.3	C15—C16—H16C	109.5
C6—C7—H7B	108.3	H16A—C16—H16C	109.5
H7A—C7—H7B	107.4	H16B—C16—H16C	109.5
C7—C8—C9	114.06 (11)	C12—C17—H17A	109.5
C7—C8—H8A	108.7	C12—C17—H17B	109.5
C9—C8—H8A	108.7	H17A—C17—H17B	109.5
C7—C8—H8B	108.7	C12—C17—H17C	109.5
C9—C8—H8B	108.7	H17A—C17—H17C	109.5
H8A—C8—H8B	107.6	H17B—C17—H17C	109.5
O3—C9—O1	108.78 (10)
C9—O3—O4—C1	45.64 (12)	O4—O3—C9—C8	48.52 (12)
O3—O4—C1—C10	15.48 (13)	C10—O1—C9—O3	31.99 (14)
O3—O4—C1—C2	134.33 (10)	C10—O1—C9—C14	144.59 (11)
O3—O4—C1—C6	−107.17 (10)	C10—O1—C9—C8	−90.91 (12)
O4—C1—C2—C3	162.62 (10)	C7—C8—C9—O3	−95.86 (13)
C10—C1—C2—C3	−79.19 (13)	C7—C8—C9—O1	25.20 (14)
C6—C1—C2—C3	48.60 (14)	C7—C8—C9—C14	145.62 (12)
O4—C1—C2—C12	−68.02 (12)	C9—O1—C10—O2	−93.06 (11)
C10—C1—C2—C12	50.16 (12)	C9—O1—C10—C1	30.57 (14)
C6—C1—C2—C12	177.96 (10)	C11—O2—C10—O1	176.80 (9)
C1—C2—C3—C4	−52.31 (14)	C11—O2—C10—C1	53.70 (13)
C12—C2—C3—C4	−178.73 (10)	O4—C1—C10—O1	−55.59 (13)
C2—C3—C4—C5	58.53 (14)	C2—C1—C10—O1	−170.00 (10)
C3—C4—C5—C13	175.80 (11)	C6—C1—C10—O1	62.68 (12)
C3—C4—C5—C6	−59.90 (14)	O4—C1—C10—O2	63.33 (12)
C4—C5—C6—C7	−175.83 (11)	C2—C1—C10—O2	−51.08 (12)
C13—C5—C6—C7	−51.70 (14)	C6—C1—C10—O2	−178.40 (9)
C4—C5—C6—C1	56.44 (13)	C15—O5—C11—O2	61.59 (14)
C13—C5—C6—C1	−179.43 (10)	C15—O5—C11—C12	−173.97 (11)
O4—C1—C6—C7	69.20 (12)	C10—O2—C11—O5	69.63 (13)
C10—C1—C6—C7	−51.41 (13)	C10—O2—C11—C12	−53.74 (14)
C2—C1—C6—C7	−178.04 (10)	O5—C11—C12—C17	57.32 (15)
O4—C1—C6—C5	−163.99 (9)	O2—C11—C12—C17	−178.03 (11)
C10—C1—C6—C5	75.39 (12)	O5—C11—C12—C2	−72.01 (13)
C2—C1—C6—C5	−51.23 (13)	O2—C11—C12—C2	52.64 (14)
C5—C6—C7—C8	−164.04 (11)	C3—C2—C12—C11	75.94 (13)
C1—C6—C7—C8	−36.68 (15)	C1—C2—C12—C11	−51.80 (13)
C6—C7—C8—C9	56.69 (15)	C3—C2—C12—C17	−52.41 (15)
O4—O3—C9—O1	−73.25 (12)	C1—C2—C12—C17	179.85 (10)
O4—O3—C9—C14	172.50 (10)	C11—O5—C15—C16	166.33 (13)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O4i	1.00	2.45	3.3150 (15)	144
C7—H7A···O4i	0.99	2.55	3.4704 (16)	155

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5A⋯O4i	1.00	2.45	3.3150 (15)	144
C7—H7A⋯O4i	0.99	2.55	3.4704 (16)	155

Symmetry code: (i) .